chr14-35071558-G-T

Position:

• chr14-35071558-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173607.5(FAM177A1):​c.340-5592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 150,902 control chromosomes in the GnomAD database, including 492 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.071 (492 hom., cov: 31)
• Consequence: FAM177A1 NM_173607.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

Genes affected

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM177A1	NM_173607.5	c.340-5592G>T		intron_variant		ENST00000280987.9	NP_775878.2
FAM177A1	NM_001079519.1	c.271-5592G>T		intron_variant			NP_001072987.1
FAM177A1	NM_001289022.3	c.271-5592G>T		intron_variant			NP_001275951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9	c.340-5592G>T		intron_variant		1	NM_173607.5	ENSP00000280987	A2

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10692 AN: 150784 Hom.: 493 Cov.: 31

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.0683

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0708 AC: 10687 AN: 150902 Hom.: 492 Cov.: 31 AF XY: 0.0685 AC XY: 5044 AN XY: 73678

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.0672

Gnomad4 EAS AF: 0.00137

Gnomad4 SAS AF: 0.0998

Gnomad4 FIN AF: 0.0537

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0912 Hom.: 311

Bravo AF: 0.0685

Asia WGS AF: 0.0460 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17595975; hg19: chr14-35540764;